Microbial infections affect human beings and animals and cause a high level of morbidity around the world. Microbial infectious agents include protozoan parasites, bacteria and fungi for which antimicrobial agents are often available. However, some antimicrobial agents are associated with undesirable side effects and the problem of microbial resistance to such agents is a growing problem.
Microbial infectious agents also include viruses which are the cause of many widespread infectious diseases afflicting mankind as well as mankind's companion animals and also animals farmed specifically for human food. Most of the presently available antiviral drugs used in human therapeutic applications are mono-functional in nature and block only one specific viral pathway such as for example, entry of the virus into the host cell, fusion or integration of the viral genome into the host cell genome, translation or reverse transcription of the viral ssRNA to dsDNA format that is viable for integration into the infected host-cell genome. Accordingly, once a virus acquires resistance to the mono-functional antiviral drug, the drug loses its effectiveness.
Also, at present no therapeutics are available for a number of animal viruses including for example White Spot Syndrome Virus (WSSV), Porcine Epidemic Diarrhoea Virus (PEDV), Porcine Reproductive & Respiratory Syndrome Virus (PRRSV) and the like. These animal viruses are known to particularly affect the prawn and swine industries. The annual loss caused by each of these viruses is believed to be in excess of USD 1 billion.
Effective vaccines for these viruses and most other viruses are difficult to develop due to their high mutation rate. Also, vaccines that work for one geographical strain often do not work well for other geographical strains of the same virus.
Examples of antiviral drugs include Enfuvirtide (marketed by Roche under the trade name FUZEON®) which is a HIV-1 fusion inhibitor. Enfuvirtide is a modified protein which is produced by synthesis and is known to be an expensive mode of treatment which is reported to be in the region of USD25,000 per year per person. Its mode of administration is also very inconvenient as it is introduced into the body by subcutaneous injection twice daily.
Another example of antiviral drug includes Oseltamivir (also known with its trade name TAMIFLU®) which slows the spread of influenza (flu) virus between cells in the body by stopping the virus from chemically cutting ties with its host cell. TAMIFLU® has been used to treat and prevent Influenza virus A and Influenza virus B infection in over 50 million people since 1999 and is taken orally in capsules or as a suspension. However, there are now many strains of Influenza virus A and Influenza virus B which are resistant to TAMIFLU®. Zanamivir (also known by its trade name RELENZA®), another antiviral drug acting as a neuraminidase inhibitor used in the treatment and prophylaxis of Influenza virus A and Influenza virus B. RELENZA® is administered by inhalation. It is well known in the art that the antiviral drugs TAMIFLU® and RELENZA® depend on raw material shikimic acid for production which cannot be economically synthesized. In fact, ROCHE has made several press releases before that production volume of antiviral drugs TAMIFLU® and RELENZA® may be seriously limited by the supply of shikimic acid.